TY - JOUR
T1 - Witnessed apneas are associated with elevated tau-PET levels in cognitively unimpaired elderly
AU - Carvalho, Diego Z.
AU - StLouis, Erik K.
AU - Schwarz, Christopher G.
AU - Lowe, Val J.
AU - Boeve, Bradley F.
AU - Przybelski, Scott A.
AU - Reddy, Ashritha
AU - Mielke, Michelle M.
AU - Knopman, David S.
AU - Petersen, Ronald C.
AU - Jack, Clifford R.
AU - Vemuri, Prashanthi
N1 - Funding Information:
This work was supported by NIH grants U01 AG006786 (principal investigator [PI]: R.C. Petersen), R01 NS097495 (PI: P. Vemuri), R01 AG056366 (PI: P. Vemuri), P50 AG016574 (PI: R.C. Petersen), R37 AG011378 (PI: C.R. Jack), R01 AG041851 (PIs: C.R. Jack and D.S. Knopman), and R01 AG034676 (Rochester Epidemiology Project PI: W.A. Rocca); a Gerald and Henrietta Rauenhorst Foundation grant, the Millis family, the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Foundation, the Alzheimer’s Association (Zenith Fellows Award), the Liston Award, the Elsie and Marvin Dekelboum Family Foundation, the Schuler Foundation, and Opus building NIH grant C06 RR018898.
Funding Information:
D.Z. Carvalho reports no disclosures. E. St. Louis serves on the Adverse Events Adjudication committees and Data Safety Monitoring Board for Inspire, Inc and has received research support from Mayo Clinic Center for Clinical and Translational Science, NIH, the Michael J. Fox Foundation, and Sunovion, Inc. C.G. Schwarz received research funding from the NIH. V.J. Lowe consults for Bayer Schering Pharma, Piramal Life Sciences, and Merck Research and receives research support from GE Healthcare, Siemens Molecular Imaging, and AVID Radiopharmaceuticals. B.F. Boeve has served as an investigator for clinical trials sponsored by GE Healthcare, FORUM Pharmaceuticals, and C2N Diagnostics. He receives royalties from the publication of Behavioral Neurology of Dementia (Cambridge Medicine, 2009). He serves on the Scientific Advisory Board of the Tau Consortium. He has consulted for Isis Pharmaceuticals. He receives research support from the NIH (U01 AG045390, U54 NS092089, P50 AG016574, UO1 AG006786, RO1 AG041797) and the Mangurian Foundation. S.A. and A. Reddy report no disclosures. M.M. Mielke served as a consultant to Eli Lilly and received unrestricted research grants from Biogen and Lundbeck. D.S. Knopman serves on a Data Safety Monitoring Board for the Dominantly Inherited Alzheimer Network (DIAN) study and is an investigator in clinical trials sponsored by Biogen, Lilly Pharmaceuticals, and the University of Southern California. R.C. Petersen consults for Roche, Inc, Merck, Inc, Genentech, Inc, and Biogen, Inc, and GE Healthcare and receives royalties from Oxford University Press for the publication of Mild Cognitive Impairment. C.R. Jack consults for Lily and serves on an independent data monitoring board for Roche, but he receives no personal compensation from any commercial entity. P. Vemuri receives research funding from NIH (National Institute on Aging and National Institute of Neurological Disorders and Stroke). Go to Neurology.org/N for full disclosures.
PY - 2020/4/28
Y1 - 2020/4/28
N2 - ObjectiveTo assess whether informant-reported apneas during sleep (witnessed apneas) in cognitively unimpaired (CU) elderly persons are associated with higher levels of brain tau.MethodsFrom the population-based Mayo Clinic Study of Aging, we identified 292 CU elderly ≥65 years of age with both AV-1451 tau-PET and Pittsburgh compound B (PiB)-PET scans and whose bed partners and close relatives had completed a questionnaire that assessed whether participants had witnessed apneas during sleep. For this cross-sectional analysis, we selected the entorhinal and inferior temporal cortices as our regions of interest (ROIs) because they are highly susceptible to tau accumulation. PET signal was scaled to the cerebellum crus to calculate standardized uptake value ratio (SUVR). We fit linear models to assess the association between regional tau and witnessed apneas while controlling for age, sex, years of education, body mass index, hypertension, hyperlipidemia, diabetes, reduced sleep, excessive daytime sleepiness, and global PiB.ResultsForty-three participants (14.7%) were found to have witnessed apneas during sleep. The report of witnessed apneas was associated with higher tau-PET SUVR elevation in our ROIs: 0.049 SUVR (95% confidence interval [CI] 0.010-0.087, p = 0.015) in the entorhinal cortex and 0.037 SUVR (95% CI 0.006-0.067, p = 0.019) in the inferior temporal cortex after controlling for confounders.ConclusionWe identified a significant association between witnessed apneas in CU elderly and elevated tau-PET signal in tau-susceptible brain regions. These results suggest a plausible mechanism that could contribute to cognitive impairment and the development of Alzheimer disease. Longitudinal observations are necessary to determine direction of causality.
AB - ObjectiveTo assess whether informant-reported apneas during sleep (witnessed apneas) in cognitively unimpaired (CU) elderly persons are associated with higher levels of brain tau.MethodsFrom the population-based Mayo Clinic Study of Aging, we identified 292 CU elderly ≥65 years of age with both AV-1451 tau-PET and Pittsburgh compound B (PiB)-PET scans and whose bed partners and close relatives had completed a questionnaire that assessed whether participants had witnessed apneas during sleep. For this cross-sectional analysis, we selected the entorhinal and inferior temporal cortices as our regions of interest (ROIs) because they are highly susceptible to tau accumulation. PET signal was scaled to the cerebellum crus to calculate standardized uptake value ratio (SUVR). We fit linear models to assess the association between regional tau and witnessed apneas while controlling for age, sex, years of education, body mass index, hypertension, hyperlipidemia, diabetes, reduced sleep, excessive daytime sleepiness, and global PiB.ResultsForty-three participants (14.7%) were found to have witnessed apneas during sleep. The report of witnessed apneas was associated with higher tau-PET SUVR elevation in our ROIs: 0.049 SUVR (95% confidence interval [CI] 0.010-0.087, p = 0.015) in the entorhinal cortex and 0.037 SUVR (95% CI 0.006-0.067, p = 0.019) in the inferior temporal cortex after controlling for confounders.ConclusionWe identified a significant association between witnessed apneas in CU elderly and elevated tau-PET signal in tau-susceptible brain regions. These results suggest a plausible mechanism that could contribute to cognitive impairment and the development of Alzheimer disease. Longitudinal observations are necessary to determine direction of causality.
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U2 - 10.1212/WNL.0000000000009315
DO - 10.1212/WNL.0000000000009315
M3 - Article
C2 - 32217775
AN - SCOPUS:85084740121
VL - 94
SP - E1793-E1802
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 17
ER -